INSTRUCTIONS FOR USE

CREA Creatinine

VITROS Chemistry Products CREA Slides

680 2584 Rx ONLY

Intended Use

For in vitro diagnostic use only. VITROS Chemistry Products CREA Slides quantitatively measure creatinine (CREA) concentration in serum, plasma, and urine using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System.

Summary and Explanation of the Test Serum creatinine and urinary creatinine excretion is a function of lean body mass in normal persons and shows little or no response to dietary changes. The serum creatinine concentration is higher in men than in women. Since urinary creatinine is excreted mainly by glomerular filtration, with only small amounts due to tubular secretion, serum creatinine and a 24-hour urine creatinine excretion can be used to estimate the glomerular filtration rate. Serum creatinine is increased in acute or chronic renal failure, urinary tract obstruction, reduced renal blood flow, shock, dehydration, and rhabdomyolysis. Causes of low serum creatinine concentration include debilitation and decreased muscle mass. Exercise may cause an increased creatinine clearance. The creatinine clearance rate is unreliable if the urine flow is low.

Principles of the Procedure The VITROS CREA Slide method is performed using the VITROS CREA Slides and the VITROS Chemistry Products Calibrator Kit 1 on VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System. The VITROS CREA Slide is a multilayered, analytical element coated on a polyester support. A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Creatinine diffuses to the reagent layer, where it is hydrolyzed to creatine in the rate-determining step. The creatine is converted to sarcosine and urea by creatine amidinohydrolase. The sarcosine, in the presence of sarcosine oxidase, is oxidized to glycine, formaldehyde, and hydrogen peroxide. The final reaction involves the peroxidase-catalyzed oxidation of a leuco dye to produce a colored product. Following addition of the sample, the slide is incubated. During the initial reaction phase, endogenous creatine in the sample is oxidized. The resulting change in reflection density is measured at 2 time points. The difference in reflection density is proportional to the concentration of creatinine present in the sample.

Test Type and Conditions Test Type Two-point rate

VITROS System 5600, 4600, 5,1 FS, 950, 250/350

Approximate Incubation Time 5.0 minutes

Temperature

Wavelength

Reaction Sample Volume

37 °C (98.6 °F)

670 nm

6 µL

Not all products and systems are available in all countries.

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INSTRUCTIONS FOR USE

Creatinine

Warnings and Precautions

Reaction Scheme creatinine amidohydrolase

creatinine + H2O

creatine

creatine amidinohydrolase

creatine + H2O sarcosine + O2 + H2O

sarcosine oxidase peroxidase

H2O2 + leuco dye

sarcosine + urea glycine + formaldehyde + H2O2 dye + 2H2O

Warnings and Precautions

For in vitro diagnostic use only. WARNING:

Take care when handling materials and samples of human origin. Since no test method can offer complete assurance that infectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens, solid and liquid waste, and test components in accordance with local regulations and CLSI Guideline M29 1 or other published biohazard safety guidelines.

For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the Instructions for Use for the appropriate VITROS product, or to other manufacturer’s product literature.

Reagents Slide Diagram

Slide Ingredients Reactive Ingredients per cm2

Creatinine amidohydrolase (Flavobacterium sp., E.C.3.5.2.10) 0.20 U; creatine amidinohydrolase (Flavobacterium sp., E.C. 3.5.3.3.) 4.7 U; sarcosine oxidase (Bacillus sp., E.C.1.5.3.1) 0.55 U; peroxidase (horseradish root, E.C.1.11.1.7) 1.6 U and 2-(3,5dimethoxy-4-hydroxyphenyl)-4,5-bis(4-dimethylaminophenyl) imidazole (leuco dye) 32 µg.

1. Upper slide mount 2. Spreading layer (TiO2) 3. Reagent layer • • • • • •

creatinine amidohydrolase creatine amidinohydrolase sarcosine oxidase peroxidase leuco dye buffer, pH 7.0

4. Support layer 5. Lower slide mount

Other Ingredients

Pigment, binders, surfactants, stabilizer, scavenger, chelator, buffer, dye solubilizer and cross-linking agent.

Reagent Handling Caution: • •

Do not use slide cartridges with damaged or incompletely sealed packaging.

Inspect the packaging for signs of damage. Be careful when opening the outer packaging with a sharp instrument so as to avoid damage to the individual product packaging.

Reagent Preparation IMPORTANT:

The slide cartridge must reach room temperature, 18–28 °C (64–82 °F), before it is unwrapped and loaded into the slide supply.

1. Remove the slide cartridges from storage. 2. Warm the wrapped cartridge at room temperature for 30 minutes when taken from the refrigerator or 60 minutes from the freezer. 3. Unwrap and load the cartridge into the slide supply. Note:

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Load the cartridges within 24 hours after they reach room temperature, 18–28 °C (64–82 °F).

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Reagent Storage and Stability

Creatinine

Reagent Storage and Stability VITROS CREA Slides are stable until the expiration date on the carton when they are stored and handled as specified. Do not use beyond the expiration date. Reagent Unopened Opened

Refrigerated Frozen On-analyzer On-analyzer

Storage Condition 2–8 °C (36–46 °F) ≤-18 °C (≤0 °F) System turned on System turned off

Stability ≤ 4 weeks Until expiration date ≤ 2 weeks ≤ 2 hours

Verify performance with quality control materials: • If the system is turned off for more than 2 hours. • After reloading cartridges that have been removed from the slide supply and stored for later use.

Specimen Collection, Preparation and Storage Specimens Recommended • •

Serum Plasma 2: Heparin Urine

•

IMPORTANT:

Certain collection devices have been reported to affect other analytes and tests. 3 Owing to the variety of specimen collection devices available, Ortho-Clinical Diagnostics is unable to provide a definitive statement on the performance of its products with these devices. Confirm that your collection devices are compatible with this test.

Specimens Not Recommended Do not use specimens obtained through catheters used to infuse hyperalimentation fluid. Refer to “Limitations of the Procedure.”

Serum and Plasma Specimen Collection and Preparation Collect specimens using standard laboratory procedures. 4, Note:

5

For details on minimum fill volume requirements, refer to the operating instructions for your system.

Patient Preparation No special patient preparation is necessary. Special Precautions Centrifuge specimens and remove the serum or plasma from the cellular material within 4 hours of collection. 6

Specimen Handling and Storage • •

Handle and store specimens in stoppered containers to avoid contamination and evaporation. Mix samples by gentle inversion and bring to room temperature, 18–28 °C (64–82 °F), prior to analysis.

Specimen Storage and Stability: Serum and Plasma 6 Storage Room temperature Refrigerated Frozen

Temperature 18–28 °C (64–82 °F) 2–8 °C (36–46 °F) ≤-18 °C (≤0 °F)

Stability ≤ 5 days ≤ 30 days Indefinite

Urine Specimen Collection and Preparation • •

Collect specimens using standard laboratory procedures. 7 Keep refrigerated until analysis. Note:

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For details on minimum fill volume requirements, refer to the operating instructions for your system.

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Creatinine

Specimen Pretreatment

Patient Preparation No special patient preparation is necessary. Special Precautions Urine specimens must be pretreated prior to processing. Refer to “Specimen Pretreatment” for instructions.

Specimen Handling and Storage • •

Handle and store specimens in stoppered containers to avoid contamination and evaporation. Mix samples by gentle inversion and bring to room temperature, 18–28 °C (64–82 °F), prior to analysis.

Specimen Storage and Stability: Urine 6 Storage Room temperature Refrigerated Frozen

Temperature 18–28 °C (64–82 °F) 2–8 °C (36–46 °F) ≤-18 °C (≤0 °F)

Stability ≤ 3 days ≤ 5 days Indefinite

Specimen Pretreatment Urine Predilution IMPORTANT:

If using a VITROS 250/350 or 5,1 FS/4600 Chemistry System or VITROS 5600 Integrated System in On-Analyzer Dilution Mode, do not manually dilute samples for analysis and do not multiply by a dilution factor after analysis. Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure.

1. Mix 1 part sample with 20 parts of reagent-grade water. 2. Analyze. 3. Multiply the results by 21 to obtain the creatinine concentration in the original urine sample.

Testing Procedure Materials Provided VITROS Chemistry Products CREA Slides

Materials Required but Not Provided • • • • • •

VITROS Chemistry Products Calibrator Kit 1 Quality control materials, such as VITROS Chemistry Products Performance Verifier I and II for serum and plasma VITROS Chemistry Products 7% BSA Reagent-grade water VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) (for on-analyzer dilution of serum and plasma samples) VITROS Chemistry Products FS Diluent Pack 3 (Specialty Diluent/Water) (for on-analyzer dilution of urine samples)

Operating Instructions • •

Check reagent inventories at least daily to ensure that quantities are sufficient for the planned workload. For additional information, refer to the operating instructions for your system.

IMPORTANT:

Bring all fluids and samples to room temperature, 18–28 °C (64–82 °F), prior to analysis.

Sample Dilution Serum and Plasma

If creatinine concentrations exceed the system’s measuring (reportable or dynamic) range or if the analyzer displays a DP code (indicating high background density, usually due to an elevated creatine concentration):

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Calibration

Creatinine

Manual Sample Dilution 1. Dilute the sample with VITROS 7% BSA. 2. Reanalyze. 3. Multiply the results by the dilution factor to obtain an estimate of the original sample’s creatinine concentration. On-Analyzer Sample Dilution (VITROS Integrated, VITROS 5,1 FS/4600 and VITROS 250/350 Systems only) Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure. For VITROS Integrated and VITROS 5,1 FS/4600 Chemistry Systems, use VITROS Chemistry Products FS Diluent Pack 2 for the dilution.

Urine

If creatinine concentrations exceed the system’s measuring (reportable or dynamic) range:

VITROS 250/350 and VITROS 950 Systems 1. Mix 1 part prediluted sample with 1 part reagent-grade water. 2. Reanalyze. 3. Multiply the results by the dilution factor to obtain an estimate of the creatinine concentration in the original sample. On-Analyzer Sample Dilution (VITROS Integrated and VITROS 5,1 FS/4600 Systems only) Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure. Use VITROS Chemistry Products FS Diluent Pack 3 for the dilution.

Calibration Required Calibrators VITROS Chemistry Products Calibrator Kit 1 Note:

The same VITROS Calibrator Kit is used to calibrate serum, plasma, and urine creatinine. However, specific supplementary assigned values (SAVs) are applied for each body fluid.

Calibrator Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Calibrator Kit 1.

Calibration Procedure Refer to the operating instructions for your system.

When to Calibrate Calibrate: • When the slide lot number changes. • When critical system parts are replaced due to service or maintenance. • When government regulations require. For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months. The VITROS CREA test may also need to be calibrated: • If quality control results are consistently outside acceptable range. • After certain service procedures have been performed. For additional information, refer to the operating instructions for your system.

Calculations Reflectance from the slide is read at 670 nm at two fixed time points during the incubation period, and the change in reflectance between these two readings is calculated. Once a calibration has been performed for each slide lot, creatinine concentration in unknown samples can be determined using the software-resident two-point rate math model and the change in reflectance calculated for each unknown test slide.

Validity of a Calibration Calibration parameters are automatically assessed by the system against a set of quality parameters detailed in the Coefficients and Limits screen on VITROS 250/350/950 Systems (on the VITROS Integrated and VITROS 5,1 FS/4600 Systems, see the Review Assay Data screen). Failure to meet any of the pre-defined quality parameters results in a failed calibration. The calibration report should be used in conjunction with quality control results to determine the validity of a calibration.

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Creatinine

Quality Control

Measuring (Reportable or Dynamic) Range Conventional Units (mg/dL) 0.05–14.0 1.2–346.5*

Serum Urine *After

SI Units (μmol/L) 4–1238 106–30631*

Alternate Units (mg/L) 0.5–140 12.0–3465*

multiplying by a dilution factor of 21.

For out-of-range samples, refer to “Sample Dilution.”

Traceability of Calibration The values assigned to the VITROS Chemistry Products Calibrator Kit 1 for Creatinine are traceable to a Gas Chromatography Isotope Dilution Mass Spectrometry (GC/IDMS) method 8 and National Institute of Standards and Technology (NIST) SRM® 914 creatinine standard reference material.

Quality Control Quality Control Material Selection IMPORTANT:

• •

• •

VITROS Performance Verifiers are recommended for use with VITROS Chemistry and Integrated Systems. Evaluate the performance of other commercial control fluids for compatibility with this test before using for quality control.

Controls that are reconstituted with deionized water should perform acceptably. Control materials other than VITROS Performance Verifiers may show a difference when compared with other creatinine methods if they: – Depart from a true human matrix. – Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives. Liquid serum and urine controls often contain high creatine levels and may give DP codes. Do not use control materials stabilized with ethylene glycol.

Urine

For urine specimens, use commercially available urine control materials.

IMPORTANT:

If using a VITROS 250/350 or 5,1 FS/4600 Chemistry System or VITROS 5600 Integrated System in On-Analyzer Dilution Mode, do not manually dilute samples for analysis and do not multiply by a dilution factor after analysis. Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure.

Quality Control Procedure Recommendations • • •

• • •

Choose control levels that check the clinically relevant range. Analyze quality control materials in the same manner as patient samples, before or during patient sample processing. To verify system performance, analyze control materials: – After calibration. – According to local regulations or at least once each day that the test is being performed. – After specified service procedures are performed. Refer to the operating instructions for your system. If control results fall outside your acceptable range, investigate the cause before deciding whether to report patient results. For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Third Edition 9 or other published guidelines. For additional information, refer to the operating instructions for your system.

Quality Control Material Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Chemistry Products Performance Verifier I and II or to other manufacturer's product literature.

Results Reporting Units and Unit Conversion The VITROS Chemistry and Integrated Systems may be programmed to report creatinine results in conventional, SI, and alternate units.

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Limitations of the Procedure

Conventional Units mg/dL

Creatinine SI Units µmol/L (mg/dL x 88.4)

Alternate Units mg/L (mg/dL x 10)

Limitations of the Procedure Known Interferences Serum and Plasma •

• •

•

Creatine: At a creatinine concentration of 1.5 mg/dL (133 µmol/L), creatine greater than 8 mg/dL (707 µmol/L) will be flagged with a DP code (because highly elevated creatine concentrations may cause excessive background density). For unflagged samples, residual bias because of creatine will be less than 0.15 mg/dL (13 µmol/L). At a creatinine concentration of 14 mg/dL (1237 µmol/L), creatine greater than 1 mg/dL (88 µmol/L) will be flagged with a DP code. Residual bias for unflagged samples will be less than 2%. Refer to “Sample Dilution” for dilution instructions. Proline: Patients receiving hyperalimentation fluids containing proline may show an increase of 0.2 mg/dL (18 µmol/L). Do not collect specimens from intravenous fluid lines contaminated with hyperalimentation fluid. Dobutamine: Specimens contaminated with dobutamine from intravenous fluid have been reported to show a significant negative bias. A dobutamine concentration of 83 µg/mL caused a decrease of 2.7 mg/dL (239 µmol/L) from an initial creatinine concentration of 4.8 mg/dL (424 µmol/L). 12 Lidocaine: Patients on long-term lidocaine therapy may show an increase of up to 1.0 mg/dL (88 µmol/L) due to a metabolite of lidocaine, N-ethyl glycine (NEG). 13

The VITROS CREA Slide method was screened for interfering substances following CLSI Protocol EP07. 14, 15 The substances listed in the table, when tested at the concentrations indicated, caused the bias shown. For substances that were tested and did not interfere, refer to “Specificity.” Creatinine Concentration Interferent*

Dipyrone (Metamizol)

N-Acetylcysteine

Hemoglobin

Interferent Concentration

Comments

1.5 mg/dL

42.5 μmol/L

Oral Therapeutic***

4.5 mg/dL

127.5 μmol/L

3X Oral Therapeutic

6.0 mg/dL

170 μmol/L

IV Therapeutic****

18.0 mg/dL

510 μmol/L

3X IV Therapeutic

5.0 mg/dL

0.31 mmol/L

Therapeutic Oral or IV

15.0 mg/dL

0.92 mmol/L

3X Therapeutic Oral or IV

55.42 mg/dL

3.4 mmol/L

166.26 mg/dL 900 mg/dL

Bias**

Conv. (mg/dL)

SI (μmol/L)

Conv. (mg/dL)

SI (μmol/L)

1.5

133

-0.01

0

4.9

433

-0.04

-3

1.4

124

-0.06

-5

4.8

424

-0.13

-12

1.4

124

-0.06

-5

4.7

415

-0.20

-18

1.2

106

-0.24

-21

4.2

371

-0.73

-64

1.5

133

-0.04

-3

4.9

433

-0.06

-5

1.4

124

-0.07

-6

4.8

424

-0.13

-12

Therapeutic for Acetaminophen Overdose

1.2

106

-0.31

-27

4.4

389

-0.63

-55

10.4 mmol/L

3X Therapeutic for Acetaminophen Overdose

1.0

88

-0.56

-49

3.8

336

-1.25

-111

9 g/L

NA

1.5

133

-0.1

-9

*

It is possible that other interfering substances may be encountered. These results are representative; however, your results may differ somewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable.

**

The bias is an estimate of the maximum difference observed.

***

Based on oral doses of up to 1000 mg. 16, 17

****

Based on 1000 mg intravenous dose. 18

Based on intravenous doses up to 600 mg 19 and including oral doses of up to 1200 mg. 20 Based on CLSI Protocol EP07. 15

Other Limitations

Certain drugs and clinical conditions are known to alter creatinine concentration in vivo. For additional information, refer to one of the published summaries. 21, 22

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Creatinine

Expected Values

Expected Values If using results to calculate an estimated glomerular filtration rate (eGFR), confirm that you are using the appropriate MDRD (Modification of Diet in Renal Disease) equation. 10

IMPORTANT:

Reference Interval The serum reference intervals are the central 95% of results from an external study of apparently healthy adults (serum: 180 males and 180 females). The urine reference intervals are based on a separate external study. 11

Serum Male Female Urine Male Female *Creatinine

Conventional Units

SI Units

Alternate Units

0.66–1.25 mg/dL 0.52–1.04 mg/dL

58–110 µmol/L 46–92 µmol/L

6.6–12.5 mg/L 5.2–10.4 mg/L

1000–2000 mg/day* 800–1800 mg/day*

8840–17680 µmol/day** 1000–2000 mg/day*** 7072–15912 µmol/day** 800–1800 mg/day***

concentration (mg/dL) x 24-hour volume (dL) = mg/day.

**Creatinine

concentration (µmol/L) x 24-hour volume (L) = µmol/day.

***Creatinine

concentration (mg/L) x 24-hour volume (L) = mg/day.

Each laboratory should confirm the validity of these intervals for the population it serves.

Performance Characteristics Method Comparison The plots and tables below show the results of a method comparison study with serum samples and urine samples analyzed on the VITROS 950 Chemistry System, and with the Ortho-Clinical Diagnostics, Inc. comparative method (an HPLC method), 24 which has demonstrated equivalence to the Gas Chromatography Isotope Dilution Mass Spectometry (GC/IDMS) reference method. The tables also show the results of comparisons with serum and urine samples between the VITROS 5,1 FS and the VITROS 950 Chemistry Systems and between the VITROS 250/350 and the VITROS 950 Chemistry Systems. In addition, the tables show the results of comparisons with serum, plasma and urine samples between the VITROS 5600 Integrated System and the VITROS 5,1 FS Chemistry System. Testing followed NCCLS protocol EP9. 23

Serum Conventional Units

VITROS 950 System (mg/dL)

VITROS 950 System (µmol/L)

SI Units

Comparative Method: HPLC (mg/dL)

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Comparative Method: HPLC (μmol/L)

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CREA

Performance Characteristics

Creatinine Conventional Units (mg/dL) Range of Sample Conc.

Intercept

SI Units (µmol/L)

n

Slope

Correlation Coefficient

Sy.x

Range of Sample Conc.

950 vs. Comparative Method

Intercept

Sy.x

82

1.03

0.998

0.29–14.18

-0.03

0.16

26–1254

-2.87

14.52

250/350 vs. 950

109

0.98

1.000

0.1–13.3

+0.03

0.07

10–1172

+2.98

6.23

5,1 FS vs. 950

124

1.06

0.998

0.2–13.8

-0.001

0.16

14–1220

-0.09

13.75

5600 vs. 5,1 FS

100

1.00

1.000

0.3–12.8

-0.01

0.08

27–1132

-0.88

7.07

*

In accordance with the recommendation by the NKDEP to standardize serum creatinine measurements across IVD manufacturers, the HPLC method has demonstrated equivalence to the IDMS method. Analytical processing hardware and software algorithms on the VITROS 4600 Chemistry System are designed to the same specifications as those applied to the VITROS 5,1 FS Chemistry System. Assay performance on the VITROS 4600 System has been demonstrated to be comparable to that on the VITROS 5,1 FS System. All performance characteristics for VITROS 5,1 FS System are therefore applicable to the VITROS 4600 System.

Urine SI Units

VITROS 950 System (mg/dL)

VITROS 950 System (µmol/L)

Conventional Units

Comparative Method: HPLC (mg/dL)

Comparative Method: HPLC (μmol/L)

Conventional Units (mg/dL) Range of Sample Conc.

Intercept

SI Units (µmol/L)

n

Slope

Correlation Coefficient

Sy.x

Range of Sample Conc.

950 vs. Comparative Method

Intercept

Sy.x

75

0.96

0.999

3.67–331.81

-0.29

3.55

325–29332

-26.00

314.00

250/350 vs. 950

167

0.96

1.000

5.3–320.4

+1.79

1.84

465–28325

+158.59

162.96

5,1 FS vs. 950

167

0.98

1.000

2.9–328.4

+1.19

2.03

257–29028

+105.59

179.09

5600 vs. 5,1 FS

107

1.00

1.000

1.6–335.5

+0.18

2.26

141–29658

+15.91

199.78

Analytical processing hardware and software algorithms on the VITROS 4600 Chemistry System are designed to the same specifications as those applied to the VITROS 5,1 FS Chemistry System. Assay performance on the VITROS 4600 System has been demonstrated to be comparable to that on the VITROS 5,1 FS System. All performance characteristics for VITROS 5,1 FS System are therefore applicable to the VITROS 4600 System.

Precision Precision was evaluated with quality control materials on VITROS 250/350, 950 and 5,1 FS Systems following NCCLS Protocol EP5. 25 Precision was also evaluated with quality control materials on the VITROS 5600 Integrated System following NCCLS Protocol EP5. 26 These results are guidelines. Variables such as sample handling and storage, reagent handling and storage, laboratory environment, and system maintenance can affect reproducibility of test results.

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Creatinine

Performance Characteristics

Serum Conventional Units (mg/dL) Mean Conc. 950

250/350

5,1 FS

5600 *

Within Day SD*

Within Lab SD**

SI Units (µmol/L) Within Day SD*

Mean Conc.

Within Lab Within Lab SD** CV%**

No. Observ.

No. Days

0.37

0.010

0.015

33

0.9

1.3

4.1

84

22

0.94

0.016

0.018

83

1.4

1.6

1.9

84

22

5.10

0.065

0.077

451

5.7

6.8

1.5

84

22

13.11

0.122

0.151

1159

10.8

13.3

1.1

84

22

0.37

0.006

0.010

33

0.5

0.9

2.6

88

22

0.95

0.009

0.013

84

0.8

1.1

1.3

88

22

5.01

0.049

0.085

443

4.4

7.5

1.7

88

22

13.05

0.109

0.203

1153

9.6

18.0

1.6

88

22

0.41

0.012

0.020

36

1.0

1.8

4.8

84

22

0.92

0.015

0.020

82

1.3

1.8

2.1

88

22

5.46

0.071

0.085

483

6.2

7.5

1.6

88

22

13.58

0.098

0.133

1200

8.7

11.7

1.0

84

22

0.87

0.012

0.025

77

1.1

2.2

2.9

88

22

5.32

0.053

0.074

470

4.7

6.5

1.4

88

22

Within Day precision was determined using two runs/day with two to three replications.

**

Within Lab precision was determined using a single lot of slides and calibrating weekly.

Analytical processing hardware and software algorithms on the VITROS 4600 Chemistry System are designed to the same specifications as those applied to the VITROS 5,1 FS Chemistry System. Assay performance on the VITROS 4600 System has been demonstrated to be comparable to that on the VITROS 5,1 FS System. All performance characteristics for VITROS 5,1 FS System are therefore applicable to the VITROS 4600 System.

Urine Conventional Units (mg/dL) Mean Conc. 950

250/350

5,1 FS

5600 *

Within Day SD*

Within Lab SD**

SI Units (µmol/L) Mean Conc.

Within Day SD*

Within Lab Within Lab CV%** SD**

No. Observ.

No. Days

61.5

0.85

1.43

5441

75.2

126

2.3

84

22

82.8

0.74

1.03

7320

65.2

91

1.2

84

22

146.6

2.23

2.73

12962

196.8

241

1.9

84

22

231.9

2.18

2.85

20502

192.5

252

1.2

84

22

56.2

0.71

1.42

4969

63.2

126

2.5

88

22

78.9

0.61

1.32

6977

54.0

117

1.7

88

22

131.4

1.81

3.11

11613

159.6

275

2.4

90

22

219.3

2.23

3.89

19387

197.5

344

1.8

86

22

61.4

1.01

1.40

5424

89.7

124

2.3

88

22

81.6

0.81

1.14

7209

71.9

101

1.4

88

22

146.5

2.50

3.02

12951

221.1

267

2.1

88

22

229.9

2.39

3.19

20328

211.4

282

1.4

88

22

61.7

0.99

1.39

5454

87.5

123

2.3

80

20

157.5

2.42

3.29

13923

213.9

291

2.1

80

20

Within Day precision was determined using two runs/day with two to three replications.

**

Within Lab precision was determined using a single lot of slides and calibrating weekly.

Analytical processing hardware and software algorithms on the VITROS 4600 Chemistry System are designed to the same specifications as those applied to the VITROS 5,1 FS Chemistry System. Assay performance on the VITROS 4600 System has been demonstrated to be comparable to that on the VITROS 5,1 FS System. All performance characteristics for VITROS 5,1 FS System are therefore applicable to the VITROS 4600 System.

Specificity Substances that Do Not Interfere The substances listed in the table were tested with VITROS CREA Slides following CLSI Protocol EP07 15, 27 and found not to interfere, bias